Vinylogous and Arylogous Stereoselective Base-Promoted Phase-Transfer Catalysis

Vinylogous enolate and enolate-type carbanions, generated by deprotonation of α,β-unsaturated compounds and characterized by delocalization of the negative charge over two or more carbon atoms, are extensively used in organic synthesis, enabling functionalization and C–C bond formation at remote positions. Similarly, reactions with electrophiles at benzylic and heterobenzylic position are performed through generation of arylogous and heteroarylogous enolate-type nucleophiles. Although widely exploited in metal-catalysis and organocatalysis, it is only in recent years that the vinylogy and arylogy principles have been translated fruitfully in phase-transfer catalyzed processes. This review provides an overview of the methods developed to date, involving vinylogous and (hetero)arylogous carbon nucleophiles under phase-transfer catalytic conditions, highlighting main mechanistic aspects.

Dual-functional cobalt catalyst enables electrocatalytic allylic C–H alkylation

Transition metal-catalyzed allylic substitution reactions of pre-activated allylation agents with nucleophiles are extensively studied synthetic methods that have enjoyed widespread applications in organic synthesis. The direct alkylation of allylic C–H bonds with nucleophiles, which minimizes pre-functionalization and converts inexpensive, abundantly available materials to value-added alkenyl-substituted products, remains challenging. Current methods generally involve C–H activation, require the use of noble-metal catalysts and stoichiometric chemical oxidants, and often show limited scope. Here we report an electrocatalytic allylic C–H alkylation reaction with carbon nucleophiles employing an easily available cobalt-salen complex as the molecular catalyst. These C(sp3)–H/C(sp3)–H cross-coupling reactions proceed through H2 evolution and require no external chemical oxidants. Importantly, the mild conditions and radical mechanism ensure excellent functional group tolerance and substrate compatibility with both linear and branched terminal alkenes. The synthetic utility of the electrochemical method is highlighted by its scalability (up to 200 mmol scale) and its successful application in the late-stage functionalization of complex structures.

Mechanochemical synthesis of magnesium-based carbon nucleophiles in air and their use in organic synthesis

Since the discovery of Grignard reagents in 1900, the nucleophilic addition of magnesium-based carbon nucleophiles to various electrophiles has become one of the most powerful, versatile, and well-established methods for the formation of carbon−carbon bonds in organic synthesis. Grignard reagents are typically prepared via reactions between organic halides and magnesium metal in a solvent. However, this method usually requires the use of dry organic solvents, long reaction times, strict control of the reaction temperature, and inert-gas-line techniques. Despite the utility of Grignard reagents, these requirements still represent major drawbacks from both an environmental and an economic perspective, and often cause reproducibility problems. Here, we report the general mechanochemical synthesis of magnesium-based carbon nucleophiles (Grignard reagents in paste form) in air using a ball milling technique. These nucleophiles can be used directly for one-pot nucleophilic addition reactions with various electrophiles and nickel-catalyzed cross-coupling reactions under solvent-free conditions.

Carbodiphosphorane-Catalyzed Hydroboration of Ketones and Imines

We report the use of a cyclic carbodiphosphorane catalyst for ketone and imine hydroboration reactions. To our knowledge, this represents the first use of a carbodiphosphorane as an organocatalyst. The carbodiphospohorane shows superior catalytic activity compared to other neutral carbon nucleophiles tested.

1,4,2-Dioxazol-5-ones as Isocyanate Equivalents: An Efficient Synthesis of 2-Quinolinones via β-Keto Amides

Under thermal conditions, 1,4,2-dioxazol-5-ones are known to undergo decarboxylation followed by Lossen’s rearrangement to yield isocyanates. Described herein is the in situ trapping of the resulting isocyanates with carbon nucleophiles to synthesize β-keto amides. Furthermore, a general and mild method for the conversion of the resulting β-keto amides into quinolin-2-ones is reported.

A Platform for Alkene Carbofunctionalization with Diverse Nucleophiles

A general system achieving three-component intermolecular carbofunctionalization of alkenes is presented. A range of substituted alkenes are functionalized with α-bromo carbonyl electrophiles and nitrogen, oxygen, and carbon nucleophiles. Mechanistic findings support the intermediacy of a cyclic oxocarbenium ion.

A Platform for Alkene Carbofunctionalization with Diverse Nucleophiles

A general system achieving three-component intermolecular carbofunctionalization of alkenes is presented. A range of substituted alkenes are functionalized with α-bromo carbonyl electrophiles and nitrogen, oxygen, and carbon nucleophiles. Mechanistic findings support the intermediacy of a cyclic oxocarbenium ion.